Purpose
To describe the natural course of adult-onset foveomacular vitelliform dystrophy using spectral-domain optical coherence tomography (SD-OCT).
Design
Retrospective study.
Methods
We reviewed the charts of all consecutive patients with adult-onset foveomacular vitelliform dystrophy who underwent SD-OCT at baseline and at least 12 months later (last visit). Main outcome measures were changes of clinical and SD-OCT features over time.
Results
Forty-six eyes (31 patients, 15 male and 16 female; mean age 74.6 ± 8.2 years) were included. Follow-up was 16.2 ± 6 (range, 12–30) months. Visual acuity (VA) reduced from 0.32 ± 0.22 logMAR at baseline to 0.39 ± 0.28 logMAR at last visit ( P = .03). The stage of the disease was vitelliform in 28 eyes (60.8%), pseudohypopyon in 7 eyes (15.2%), vitelliruptive in 11 eyes (23.9%) at baseline; vitelliform in 23 eyes (50%), pseudohypopyon in 5 eyes (10.9%), vitelliruptive in 13 eyes (28.2%), and atrophic in 5 eyes (10.9%) at last visit. Stabilization of the disease stage, inner segment/outer segment (IS/OS) interface status, and lesion reflectivity on SD-OCT determined no VA changes ( P > .05), while their worsening determined a reduction of VA ( P = .03). In eyes that presented a progression of the disease stage, mean central macular thickness, maximal thickness of the lesion, and maximal width of the lesion showed a significant change (from 404.1 ± 107.6 μm to 246.1 ± 74.0 μm, P = .004; from 277.0 ± 80.8 μm to 105.3 ± 92.3 μm, P = .001; from 2324.2 ± 1250.3 μm to 1751.0 ± 858.3 μm, P = .04, respectively).
Conclusions
In adult-onset foveomacular vitelliform dystrophy, progression of the lesion stage (partial/complete resorption of the material) is generally accompanied by IS/OS interface disruption/loss and visual impairment.
Adult-onset foveomacular vitelliform dystrophy is a relatively uncommon macular disease that shares phenotypic features with Best vitelliform macular dystrophy (VMD). The clinical onset is typically between the fourth and sixth decade with subretinal deposition of yellowish material within the macula.
Adult-onset foveomacular vitelliform dystrophy is a clinically heterogeneous and pleomorphic disease displaying extreme variability in the size, shape, and distribution of the yellowish material. In any case, the yellowish material in adult-onset foveomacular vitelliform dystrophy is highly autofluorescent. The exact nature and location of the vitelliform material in adult-onset foveomacular vitelliform dystrophy has not been fully elucidated yet, either by clinical or histologic descriptions. By analyzing the autofluorescence from the outer retina and subretinal space, Spaide proposed that, at least in some cases, separation of the retina from the retinal pigment epithelium (RPE) might hinder normal outer segment phagocytosis and turnover, allowing accumulation of subretinal material. Recently, using high-resolution spectral-domain optical coherence tomography (SD-OCT), we analyzed the location and peculiar characteristics of the yellowish material in a consecutive series of adult-onset foveomacular vitelliform dystrophy patients. However, data on the natural course of adult-onset foveomacular vitelliform dystrophy are scarce, and in the era of high-resolution imaging we have no definitive information on the progressive changes, which might help in understanding the nature of the disease.
Combination of confocal scanning laser ophthalmoscopy (cSLO) and SD-OCT in Spectralis SD-OCT (Spectralis HRA+SD-OCT; Heidelberg Engineering, Heidelberg, Germany) allows for multimodal integrated imaging analysis. Moreover, real-time eye tracking technology in Spectralis SD-OCT allows not only precise orientation of the scan towards the region of interest, but also re-scanning of (approximately) the same region during follow-up. Our purpose was to analyze the natural course of adult-onset foveomacular vitelliform dystrophy (morphologic changes over time) using Spectralis SD-OCT.
Methods
We reviewed the chart of all consecutive patients who were diagnosed with adult-onset foveomacular vitelliform dystrophy, and who underwent a follow-up visit at least 12 months after baseline visit (last visit). All patients underwent a complete ophthalmologic examination, including measurement of best-corrected visual acuity (BCVA) as evaluated by Early Treatment Diabetic Retinopathy Study (ETDRS) charts, fundus biomicroscopy, and fundus autofluorescence (FAF) images. The minimal criteria for adult-onset foveomacular vitelliform dystrophy diagnosis were the presence of a macular round, yellowish, more or less homogeneous lesion at fundus examination, showing hyperautofluorescence. Exclusion criteria were presence at baseline of geographic atrophy, signs of choroidal neovascularization (CNV) or subretinal fibrosis, or any other retinal disease in the study eye such as epiretinal membrane or macular hole. Patients presenting a central spot of hyperpigmentation surrounded by a depigmentation halo without hyperautofluorescence were not included in this study. Simultaneous recording of SD-OCT and infrared reflectance or FAF imaging (Spectralis HRA+SD-OCT; Heidelberg Engineering, Heidelberg, Germany) was performed for each included eye, at both baseline visit and last visit. At least 3 horizontal line scans were placed into the lesion area (superior, middle, and inferior). SD-OCT scans were proportionally magnified for a better visualization of intraretinal changes. The central (within 500 μm from the foveal depression) FAF findings and outer retinal layer structure observed in SD-OCT images were analyzed and interpreted, independently, by 2 of the authors (G.Q. and E.S.). The following features were recorded for both baseline visit and last visit: 1) clinical stage of the disease, as proposed for typical Best VMD [a) vitelliform stage; b) pseudohypopyon stage; c) vitelliruptive stage; d) atrophic stage] based on the overall appearance of the yellowish material]; 2) central FAF [a) hyperautofluorescence; b) hypoautofluorescence; as a rule, the masking effect attributable to normal macular pigments (xanthophyll) was not considered as hypoautofluorescence in this evaluation]; 3) status of central photoreceptor inner/outer segment (IS/OS) interface [a) almost normal—no detectable IS/OS interface changes; b) disrupted; c) absent]; 4) reflectivity of the lesion on the overall SD-OCT scans analyzed [a) hyperreflective; b) hyporeflective; c) mixed hyperreflective + hyporeflective]; 5) central macular thickness measured using a 19-horizontal-lines protocol (6 × 6-mm area), each consisting of 1024 A-scans per line (Spectralis Acquisition and Viewing Modules; version 3.2, Heidelberg Engineering); 6) maximal thickness of the lesion, measured using the caliper provided with Spectralis SD-OCT software (Spectralis Acquisition and Viewing Modules, version 3.2; Heidelberg Engineering); 7) maximal width of the lesion measured using the caliper provided with Spectralis SD-OCT software (Spectralis Acquisition and Viewing Modules, version 3.2; Heidelberg Engineering); 8) presence/absence of hyperreflective drusen-like focal nodules at the level of RPE/Bruch membrane; 9) presence/absence of elevation of RPE with or without hyperreflectivity inside; 10) presence/absence of retinal pseudocysts. Disagreement regarding interpretation of the different features was resolved by open adjudication.
Statistical calculations were performed using Statistical Package for Social Sciences (version 17.0; SPSS Inc, Chicago, Illinois, USA). The paired t test was used to assess changes in mean BCVA converted to the logarithm of the minimal angle of resolution (logMAR), mean central macular thickness, mean maximal thickness of the lesion, and mean maximal width of the lesion, from baseline to last visit. The χ 2 test was used to assess changes of specific SD-OCT features from baseline to last visit. Spearman’s correlation coefficient (rho), Pearson’s coefficient, and multiple regression test were used to measure the strength of correlations among variables. Multiple regression analysis was performed to estimate the odds ratio for BCVA changes, integrity of IS/OS interface, and reflectivity of the lesion on OCT. The odds ratio is presented with 95% confidence intervals. The chosen level of statistical significance was P < .05.
Results
Patient Demographics and Clinical Changes From Baseline to Last Visit
A total of 46 eyes from 31 consecutive patients (15 male and 16 female; mean age 74.6 ± 8.2 years, range 56–87 years) were included for analysis. Macular lesions were unilateral in 3 patients. Eight eyes were excluded because of geographic atrophy and 5 eyes because of CNV. In 4 eyes of 2 patients, reticular pseudodrusen were noted as coincident findings. Mean follow-up was 16.2 ± 6 months (range 12–30 months). BCVA changed from 0.32 ± 0.22 (range 0.1–1) logMAR at baseline visit to 0.39 ± 0.28 (range 0.1–1.3) logMAR at last visit ( P = .03) ( Table 1 ).
| Baseline | Last Visit a | |
|---|---|---|
| Stage of the disease, n (%) | ||
| • Vitelliform | 28/46 (60.8) | 23/46 (50) |
| • Pseudohypopion | 7/46 (15.2) | 5/46 (10.9) |
| • Vitelliruptive | 11/46 (23.9) | 13/46 (28.2) |
| • Atrophic | 0/46 | 5/46 (10.9) |
| IS/OS interface n (%) | ||
| • Almost normal | 24 (52.2) | 19 (41.3) |
| • Disrupted | 22 (47.8) | 22 (47.8) |
| • Absent | 0 | 5 (10.9) |
| Lesion reflectivity n (%) | ||
| • Hyperreflective | 28 (60.9) | 23 (50) |
| • Mixed hyperreflective + hyporeflective | 18 (39.1) | 18 (39.1) |
| • Hyporeflective | 0 | 1 (2.2) |
| • Atrophic | — | 4 (8.7) |
| Hyperreflective nodules at the level of RPE/Bruch membrane | ||
| • Present | 19 (41.3) | 19 (41.3) |
| • Absent | 27 (58.7) | 12 (58.7) |
| Elevations of RPE (%) | ||
| • Present | 16 (34.8) | 18 (39.1) |
| • Absent | 30 (65.2) | 28 (60.9) |
| Retinal pseudocysts n (%) | 4 (8.7) | 5 (10.9) |
| BCVA logMAR | 0.32 ± 0.22 (range 0.1–1) | 0.39 ± 0.28 (range 0.1–1.3) P = .03 |
| Central macular thickness, μm | ||
| • Total | 359.6 ± 111.4 | 346.7 ± 122.6 ( P = .2) |
| • Vitelliform | 355.4 ± 93.3 | 341.9 ± 105.0 ( P = .4) |
| • Pseudohypopion | 510.7 ± 99.6 | 489.8 ± 154.7 ( P = .6) |
| • Vitelliruptive | 274.0 ± 47.8 | 268.0 ± 47.2 ( P = .4) |
| Lesion progression | 404.1 ± 107.6 | 246.1 ± 74.0 ( P = .004) |
| Mean maximal thickness of the lesion, μm | ||
| • Total | 237.8 ± 96.1 | 220.4 ± 114.6 ( P = .1) |
| • Vitelliform | 242.7 ± 78.7 | 225.5 ± 101.8 ( P = .3) |
| • Pseudohypopion | 351.8 ± 91.7 | 338.0 ± 121.8 ( P = .6) |
| • Vitelliruptive | 152.8 ± 51.7 | 135.9 ± 54.2 ( P = .4) |
| Lesion progression | 277.0 ± 80.8 | 105.3 ± 92.3 ( P = .001) |
| Mean maximal width of the lesion, μm | ||
| • total | 1605.6 ± 927.7 | 1598.4 ± 833.3 ( P = .9) |
| • vitelliform | 1619.5 ± 910.8 | 1530.7 ± 655.4 ( P = .3) |
| • pseudohypopion | 2673.6 ± 803.7 | 3025.3 ± 1012.7 ( P = .2) |
| • vitelliruptive | 1024.5 ± 487.1 | 1032.4 ± 481.8 ( P = .9) |
| Lesion progression | 2324.2 ± 1250.3 | 1751.0 ± 858.3 ( P = .04) |
a P indicates statistical significance compared to baseline.
At baseline, 28 of 46 eyes (60.8%) presented the vitelliform stage of the disease ( Figures 1 through 3 , Table 1 ); all these eyes showed central hyperautofluorescence. At last visit, 5 out of 28 eyes progressed to either the vitelliruptive stage (1 eye) or the atrophic stage (4 eyes) ( Figures 2 and 3 , Table 1 ); in these 5 eyes, a central hypoautofluorescence developed ( Figures 2 and 3 ), and mean BCVA significantly decreased from 0.4 ± 0.35 logMAR to 0.72 ± 0.39 logMAR; P = .03 ( Table 2 ).
| BCVA a Baseline | BCVA a Last Visit b | OR, 95% Confidence Interval b | |
|---|---|---|---|
| Vitelliform no progression (n = 23) | 0.26 ± 0.13 | 0.29 ± 0.15 ( P = .1) | 6.8, 0.1–0.4, P < .001 |
| From vitelliform to vitelliruptive/atrophic (n = 5) | 0.4 ± 0.35 | 0.72 ± 0.39 ( P = .05) | 12.3, 3.4–21.2, P < .001 |
| Pseudohypopyon no progression (n = 5) | 0.46 ± 0.35 | 0.38 ± 0.27 ( P = .4) | 0.3, 0.1–16, P = .001 |
| From pseudohypopyon to vitelliruptive (n = 2) | 0.40 ± 0.42 | 0.45 ± 0.35 | 3.6, 1.2–8.3, P < .001 |
| Vitelliruptive no progression (n = 10) | 0.35 ± 0.25 | 0.37 ± 0.24 ( P = .3) | 3.42, 1.60–5.25, P < .001 |
| Central photoreceptor IS/OS interface | |||
| • Overall stabilization (n = 40) | 0.32 ± 0.21 | 0.36 ± 0.25 ( P = .2) | 3.39, 1.61–4.37, P = .001 |
| • Overall progression (n = 6) | 0.40 ± 0.35 | 0.72 ± 0.39 ( P = .05) | 8.21, 2.39–15.18, P = .001 |
| • almost normal- stabilization (n = 19) | 0.24 ± 0.14 | 0.27 ± 0.15 ( P = .1) | 3.61, 1.28–5.32, P = .01 |
| • From almost normal to absent (n = 4) | 0.25 ± 0.12 | 0.57 ± 0.26 | 6.21, 3.42–18.18, P < .001 |
| • Disrupted -stabilization (n = 21) | 0.39 ± 0.24 | 0.43 ± 0.30 ( P = .4) | 4.78, 2.98–6.12, P = .01 |
| No changes of lesion reflectivity (n = 40) | 0.32 ± 0.21 | 0.33 ± 0.20 ( P = .4) | 2.21, 1.17–3.12, P = .01 |
| Changes of lesion reflectivity (n = 6) | 0.38 ± 0.31 | 0.81 ± 0.42 ( P = .03) | 7.84, 3.19–12.38, P < .001 |
a logarithm of the minimal angle of resolution (logMAR), mean ± SD.
b P indicates statistical significance compared to baseline.
At baseline, 7 of 46 eyes (15.2%) presented the pseudohypopyon stage of the disease ( Table 1 , Figure 4 ); 5 out of 7 eyes showed central hyperautofluorescence, and 2 out of 7 eyes showed central hypoautofluorescence. At last visit, 2 out of 7 eyes progressed to the vitelliruptive stage (1 of which developed central hypoautofluorescence) ( Figure 5 , Table 1 ); mean BCVA decreased from 0.40 ± 0.42 logMAR to 0.45 ± 0.35 logMAR in these 2 eyes ( Table 2 ).
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